EP1894052B1 - Method and device for laser-induced transport process of objects - Google Patents

Abstract

In relation with a laser-induced transport process of an object from a carrier to a collecting device, the invention provides a collecting medium in the collecting device in a liquid state. Prior to the laser-induced transport process, the object is separated from a mass on the carrier by laser irradiation. After the laser-induced transport process, the object, thus selected and separated, is transferred together with the collecting medium to a destination, for example, a container, for further treatment. To this end, a manipulation system for liquids is provided, the system permitting manipulation of the collecting medium with the object contained therein with a high degree of reliability and a high throughput.

Description

The present invention relates to a method and a device for handling biological or non-biological objects according to the preamble of claims 1 and 18. The objects may for example be part of a biological or non-biological mass arranged on a carrier, from which they are separated by laser irradiation, to be transported by a subsequent laser-induced transport process to a collecting medium.

For a variety of biological studies, it is necessary to dissolve individual cells or structures from a cell assemblage, such as a tissue or histological tissue preparation. This can, for example, with mechanical micro tools, z. As microcapillaries or microneedles done. However, such an approach is cumbersome and there is a risk of contamination for the liberated objects. Furthermore, such a method is difficult to automate.

In the WO 97/29355 A The Applicant has therefore proposed a novel method for sorting and recovering individual biological objects arranged on a planar support. In this case, a selected biological object is separated from the surrounding further biological mass by a laser beam, so that the selected biological object is free from the remaining biological mass. The thus prepared biological object is then transferred by means of a laser shot or laser pulse from the carrier to a collecting device by a catapulting-like process. For this purpose, the collecting device may, for example, comprise a collecting substrate to which the transferred biological object adheres. Furthermore, it is possible to place the biological object in a collecting container, for. B. a well or a well of a so-called microtiter plate to transfer. Preferably, an adhesive layer is used to fix the transferred objects to the collection substrate. As a carrier of the objects to be transferred or the biological mass from which the objects are separated out, a UV-absorbing polymer film is preferably used. However, it is also a transport of other carrier substrates, such as glass, possible.

A biological object to be separated of a biological mass applied to the carrier is thus first selected on the basis of a mapping of the biological mass, cut out of the biological mass and then transported by a laser-induced transport process to the collecting device. In the context of the present application, "biological objects" are understood to mean, in particular, living or fixed biological cells or cell components which may be part of a liquid or solid biological material, such as a cell tissue, a smear, a cell culture or the like.

With the aid of the method described above, certain objects from a biological mass can be selectively removed or rejected. The biological objects can be applied next to each other on a solid planar support, wherein the process of leaching or discarding can be performed within a short time and without contact. The survivability and morphology of the biological objects is maintained according to the chosen procedure, i. H. The biological objects are not damaged or impaired or deliberately disintegrated by the separation process and the laser-induced transport process.

Further investigation of the biological objects obtained in this way requires detachment from the collecting substrate. If the cap of a microcentrifuge tube has been selected as the collecting vessel, this can be accomplished, for example, in a subsequent centrifuging step. After detachment from the collecting substrate can then further processing, for. B. a recultivation done. The biological objects thus come in the course of processing with an additional or intermediate surface in touch. This can be particularly problematic if the intermediate surfaces include adhesive materials such as silicones, PCR oil, plastics, buffer media, etc. On the one hand, it can lead to changes and / or damage to the biological material. On the other hand, through the required detachment process, the throughput is reduced.

For the removal of living cells from a surface, aggressive solvents (eg trypsin) are usually required. This can cause changes or damage to the cells. For example, in the treatment of stem cells may lead to spontaneous differentiation processes.

In the WO 02/42824 A2 a receiving element for receiving objects is described which can be used in connection with a laser-induced transport process. The receiving element may include a receiving surface on which an adhesive liquid is applied.

The present invention is therefore based on the object, a simplified and more effective method for handling biological or non-biological objects In particular, the handled objects can be further processed with high throughput and high reliability. At the same time damage or changes to the objects should be as low as possible and contact with intermediate surfaces should be avoided.

This object is achieved by a method having the features of claim 1 and by a device having the features of claim 18. The dependent claims define preferred and advantageous embodiments of the invention.

The present invention will be described below mainly with reference to the handling of biological objects. However, the invention is equally applicable to non-biological objects (eg, inorganic matter), which may be e.g. B. can be microscopic objects made of glass, silica, plastic or artificially produced vesicles in a biological mass. Similarly, the inventively handled objects from a non-biological mass, z. As a polymer composition or the like, be dissolved out.

In the method according to the invention, an object is located on a carrier and is transported by a laser-induced transport process from the carrier to a collecting medium. The object was preferably previously cut by laser irradiation from an on-carrier mass. According to the invention, the collecting medium is in a liquid state. As a collecting medium thus different liquids can be used, which may have different viscosities, as long as a flow is possible. The flow movement can be accomplished, for example, by a pump or syringe system.

After the laser-induced transport process, the object is thus in or on the liquid collecting medium. This offers the advantage that the object can be advantageously transported together with the collecting medium for further processing. This can be done for example by an automatic liquid handling system or liquid handling system. In this way, the throughput compared to the conventional approach can be significantly increased. Contact of the object with intermediate surfaces is avoided. In particular, the collecting medium is preferably selected such that it is compatible with the further processing, so that the object comes into immediate contact with a liquid relevant for further processing. By a suitable conveying the collecting medium, the object can be directly into a target container intended for further processing, z. As a recultivation tank, transferred.

The inventive method advantageously further comprises transferring the object together with the collecting medium to a destination, for. B. in a target container. There are many advantageous possibilities for this purpose, which can be used together or in combination and ensure a high throughput. For example, the collecting medium can be made to flow or actively conveyed. Here, for example, a pumping system or surface acoustic waves on a special chip, ultrasonic movement, which z. B. is effected by a piezoelectric device, or a laser-induced increase in volume (i.e., cavity bubbles) are used. Furthermore, the collecting medium can be dispensed in drop form in a target container, wherein preferably further collecting medium from a reservoir is tracked to simultaneously cause a rinsing process and / or to fill the target container with collecting medium.

The collecting medium is held on a collecting device during the laser-induced transport process. The transfer of the object to the destination then preferably also involves moving the catcher relative to the destination. The movement of the collecting device is preferably carried out in an automated manner, for. B. by means of a correspondingly designed robot.

The device for handling objects according to the invention is preferably designed for carrying out the method described above and comprises a catching device to which the object is transported by the laser-induced transport process, a holding device for holding the carrier and a laser arrangement for effecting the laser-induced transport process. The catcher is configured to hold a catchment medium that is in a liquid state. The holding of the collecting medium on the collecting device is preferably carried out by adhesive force and / or based on the surface tension of the collecting medium forces.

Preferably, the device further comprises imaging means for generating an image of the carrier or objects located thereon. Based on the image of the carrier, it is possible to select objects, which are then transported by the laser-induced transport process to the collecting medium. This can be done manually, computer-aided or automatically based on image processing. The Imaging means are, for example, designed as an inverted or upright microscope, or comprise components generally suitable for imaging on a microscopic scale. The imaging means may also be advantageously used in monitoring the handling process.

According to the invention, the collecting device comprises a tip, on which the collecting medium is held in the form of a drop. The tip advantageously comprises an opening for dispensing the collecting medium from a reservoir. In order to provide a liquid surface of the collecting medium suitable for capturing the object, means are preferably provided by which an additional surface is provided in order to hold the collecting medium, and the shape of the liquid surface for capturing the object can be influenced in a targeted manner. For this purpose, an insert is preferably provided in the opening of the tip. Thus, according to the invention, the presented surface of the collecting medium can be specifically influenced and brought into a suitable form.

In addition, monitoring means are provided by which the collecting medium is monitored at the collecting device. The monitoring means may be designed optically and comprise, for example, a light barrier or an image processing device. Furthermore, the monitoring means can also be designed such that the monitoring takes place by means of ultrasound.

• Fig. 1 veranschaulicht schematisch den Gesamtaufbau einer Vorrichtung zur Handhabung von Objekten gemäß einem Ausführungsbeispiel der Erfindung.
• Fig. 2 veranschaulicht schematisch einen laserinduzierten Transportprozess von einem Träger zu einem flüssigen Auffangmedium.
• Fig. 3 veranschaulicht das Auffangmedium mit darin enthaltenen Objekten.
• Fig. 4 veranschaulicht ein Überführen des Auffangmediums mit den darin enthaltenen Objekten an einen Zielort.
• Fig. 5A und 5B veranschaulichen jeweils ein Beispiel für eine Auffangvorrichtung, an welcher das flüssige Auffangmedium gehalten wird.
• Fig. 6 veranschaulicht schematisch eine Überwachung des Auffangmediums.

The invention will be explained in more detail below with reference to preferred embodiments with reference to the accompanying drawings.

• Fig. 1 schematically illustrates the overall structure of an apparatus for handling objects according to an embodiment of the invention.
• Fig. 2 schematically illustrates a laser-induced transport process from a carrier to a liquid capture medium.
• Fig. 3 illustrates the collection medium with objects contained within.
• Fig. 4 illustrates a transfer of the collection medium with the objects contained therein to a destination.
• Figs. 5A and 5B each illustrate an example of a collection device to which the liquid capture medium is held.
• Fig. 6 schematically illustrates a monitoring of the collecting medium.

Fig. 1 shows the overall structure of a device for handling biological objects, which are cut out by means of laser irradiation from an on a carrier 2 located biological mass. However, the following statements can be easily transferred to the handling of non-biological objects or a non-biological mass. The device has a modular design and can be individually adapted to different experimental requirements. In the present case, the device comprises a microscope assembly with a lighting unit 11 and an image recording device 10. The microscope assembly is used in a known manner to produce an image of the carrier 2 or the objects located thereon. Instead of the illustrated inverse microscope setup, in which the image recording device 10 is located below the plane of the carrier 2, the use of an upright microscope setup would also be conceivable.

An integral part of in Fig. 1 The laser beam 6 is coupled via a mirror 9A and 9B an optics in the beam path of the microscope assembly, so that the laser beam 6 can be focused on the plane of the objects on the support 2. In the present case, a pulsed UV laser is used whose wavelength z. B. 355 nm and its pulse energy z. B. is 150 μJ. The pulse duration is 1 ns, while the pulse frequency between z. B. 1-200 pulses per second is adjustable. The laser device 7 can be realized for example by means of a nitrogen laser.

The laser device 7 emits a laser beam 6 with a fixed laser energy. The laser beam 6 is used for the purpose of a so-called laser micromanipulation and laser microdissection. For this purpose, the laser beam 6 is guided in the direction of a motorized and computer-controlled microscope stage 15, which serves as a holding device for the carrier 2. The microscope stage 15 enables exact positioning of the objects located on the carrier 2 with a precision in the nanometer range. Due to the computer-controlled motorization of the microscope stage 15, laser-based micromanipulation processes can be carried out automatically.

The motorized microscope stage 15 is movable along two linear axes (x and y direction). The minimum step size is 20 nm, so that objects located on the microscope stage 15 can be positioned with very high accuracy. The accuracy and reproducibility of the movement process can be supported or increased by an optical positioning system.

Furthermore, a robot head 14 is provided, which carries the illumination unit 11 for the microscope assembly. The illumination unit 11 preferably also includes a condenser and / or a diffuser of the microscope setup. The robotics head 14 may be further provided with a fine positioning device, which e.g. B. based on piezo actuators and allows positioning with increased precision in the nanometer range.

The robotics head 14 carries catching devices 3 for catching objects which are catapulted from the carrier 2 towards the robotic head 14 by a laser-induced transport process. The catchers 3 are movably mounted on the robotic head 14 so that they, like the microscope stage 15, can be positioned in the x and y directions. In addition, a mobility in the vertical direction or the z-direction is provided.

The robotics head 14 further comprises a gripping device 13, by means of which the carrier 2 can be gripped on the microscope stage 15. The gripping device 13 is equipped for this purpose with a suitable vertical and horizontal mobility. The gripping device 13 is thus suitable for loading and unloading the microscope stage 15 with the carrier 2. In addition, the gripping device 13 is also adapted to grab a target container 5 and to convey in a designated position.

Both the carrier 2 with the biological mass thereon and the target container 5 are stored in an incubator 20, which has a plurality of receiving positions. The accommodation positions of the incubator 20 are suitable both for the target container 5 and for the carrier 2. This is accomplished in that both the carrier 2 and the target container 5 corresponds in its outer dimensions of a standard microtiter plate or housed in a receiving device with corresponding dimensions. The incubator 20 is provided with a loading and unloading device 17, which is displaceable along a rail 16 in the vertical direction and automatically remove the carrier 2 and the target container 5 from the incubator 20 or can be inserted into this.

At the in Fig. 1 Thus, both the carrier 2 and the target container 5 can be exchanged in an automated manner. For the automated handling of the carrier 2 and the target container 5, the robot head 14 along a rail 18 is horizontally movable.

Furthermore, the device comprises a cooling container 22, in which heat-sensitive or perishable process media are housed. In particular, a liquid collecting medium or a collecting liquid is stored in the cooling container 22, which is used to collect the objects catapulted by the carrier 2. For this purpose, the liquid collecting medium is drawn up into the collecting devices 3 designed as syringes and positioned in the form of a drop with respect to the carrier 2. Due to the laser-induced transport process, an object is transported by the carrier 2 into or onto the droplets of the collecting medium at the tip of the collecting device 3. Subsequently, the tip of the collecting device 3 is positioned above the target container 5 and the object is transferred by a targeted drop-shaped discharge of the collecting medium from the tip of the collecting device 3 in the target container 5. In order to effect the drop-shaped discharge of the collecting medium from the tip of the collecting device 3, the robot head 14 is provided with a control and actuating device 12 for the collecting devices 3 designed as syringes. By means of the control and actuating device 12, for each of the collecting devices 3, a predetermined amount of collecting medium can be dispensed from an opening located at its tip, so that the drop from the collecting device 3 dissolves and preferably further collecting medium is tracked to effect a rinsing process , Of course, a jet-shaped discharge of the collecting medium is possible.

The entire arrangement of robot head 14, microscope stage 15 and target container 5 is located under a so-called laminar flow box 24, in which, for reasons of purity, a laminar flow of air is conducted over the components of the device. Preferably, however, the device is constructed such that the laminar air flow in the region below the robot head 14 is deflected, so that the laser-induced transport process is not impaired by the air flow.

The procedure for the automated handling of objects by means of the in Fig. 1 illustrated overall structure will be explained in more detail below.

First of all, objects to be separated are selected on the carrier 2 on the basis of an image of the biological mass generated on the carrier 2 by means of the microscope setup. This is preferably done computer-aided as in the WO 01/73398 A proposed by the applicant, or automatically based on electronic image processing. If necessary, the selected objects are separated from the mass on the carrier 2 by laser irradiation, ie a microdissection is performed. This is preferably done by moving the support 2 relative to the laser beam 6 by means of the microscope stage 15 so that the laser beam travels a selected area on the support to free an object contained therein. It can also be made a suitable control of the laser beam 6, for example by means of a scanning system with a so-called salvo- or prism scanner. Subsequently, the laser-induced transport process of the object from the carrier 2 to the collecting device 3 takes place. For this purpose, the laser beam is directed to a suitable target point of the object, and a laser pulse or laser shot is emitted, which transfers the object from the carrier 2 to the collecting device 3 transported. Since the transport takes place due to the irradiation with the laser beam pulse-like or catapultierartig, ie it comes after an acceleration phase to a ballistic flight, which is essentially only affected by the surrounding medium (typically air), can also by a catapulting each with the laser beam irradiated object are spoken.

Fig. 2 shows schematically the arrangement of carrier 2, thereon.befem biological mass 4 and collecting device 3 during the laser-induced transport process. As already mentioned, the laser beam 6 is directed to a suitable target point and a laser pulse or laser shot is emitted. As a result, the selected object is catapulted from the carrier 2 to the catcher 3, as indicated by the arrow in FIG Fig. 2 illustrated. The collecting device 3 is designed as a syringe in which a reservoir with collecting medium 3A is located. At the top of the collecting device 3 is an opening through which the collecting medium 3A can be discharged. During the laser-induced transport process, a certain amount of collecting medium 3A is held in the form of a drop at the tip of the collecting device 3. This drop serves as the target for the laser-induced transport process.

By automated execution of a list of positions on the carrier 2, a fixed number of objects are cut out of the mass 4 and catapulted into the drops of the collecting medium 3A. Depending on the surface tension of the collecting medium 3A and the nature of the catapulted objects can also Whereabouts of the objects on the surface of the drop take place where they adhere by adhesion.

Fig. 3 shows the drop of collecting medium 3A at the tip of the collecting device 3 with objects 4 'located therein. In this state, the catcher 3 is moved to the target container 5 by means of the robot head 14.

Fig. 4 illustrates the delivery of the objects 4 'in the target container 5. For this purpose, a predetermined amount of collecting medium is selectively discharged from the collecting device 3, so that the drop of collecting medium 3 A of the collecting device 3 dissolves and falls into the target container 5. Preferably, further collecting medium 3A is also tracked out of the collecting device 3 in order to rinse the collecting device 3 and / or to fill the target container 5 with the collecting medium 3A for a further processing step. The latter is particularly advantageous if the collecting medium 3A is compatible with the subsequent processing step or represents a preferred carrier solution for this processing step.

Below, additional steps for selecting and separating objects can be made. For this purpose, the same collecting device 3 can be used, or the receiving device 3 can be replaced. Preferably, the robotic head 14 includes a plurality of catching devices 3, which may for example be filled with different types of catching medium 3A, so that they are suitable for different subsequent processing steps.

The target container 5 can be, for example, a so-called microtiter plate with six depressions or wells, which is advantageously suitable for recultivation. Alternatively, it can also be a so-called Petriperm shell. The collecting medium 3A may be, for example, a denaturing liquid or another process liquid, e.g. A medium for living cells.

The process described above may preferably additionally include further generating images of the carrier 2 to monitor whether the laser-induced transport process was successful. For this purpose, for example, at the end of a series of microdissection processes followed by a laser-induced transport process in the image of the carrier 2, it can be checked whether the selected objects have been successfully removed. In addition, a recording of the target container 5 can be made to determine whether all selected objects have been transferred to the target container 5. In addition, optical monitoring of the collecting medium 3A preferably takes place on the collecting device 3. In this way, documentation regulations for the medical sector, such as, for example, 21CFR58.185 and 21CFR58.195, can be taken into account.

The collecting medium 3A is held on the collecting device 3 by adhesion and / or surface tension. For this purpose, the collecting device 3 is provided with a corresponding geometry. In addition, the retention of the collecting medium 3A can be influenced by the surface condition of the collecting device 3 or its tip. Possible geometries for the tip of the collecting device 3 are in FIGS. 5A and 5B shown.

Fig. 5A shows a tip which is designed to hold a drop of collecting medium 3A with an enlarged lateral extent. The increased lateral extent of the drop causes the accuracy of the laser-induced transport process to be less critical. The tip of the catcher 3 has a generally cylindrical shape, which tapers conically in an end region near the tip. The tip ends with a generally circular opening, through which the collecting medium 3A can be discharged and which serves to receive the drop of collecting medium 3A. Inside the tip is a channel for supplying the collecting medium 3A. Arranged centrally in the channel is an insert 3B, which has an end surface located in the region of the opening of the tip. The end face of the insert 3B serves as an additional holding surface for the drop of the collecting medium 3A. Furthermore, the shape of the drop of collecting medium 3A can be influenced by the positioning of the end face of the insert 3B and its shaping.

Fig. 5B shows a tip of an alternative collecting device 3 '. In this case, a substantially cylindrical configuration of the tip is provided, wherein the inner surfaces of the tubular shaped tip have a surface finish which causes the formation of an inwardly curved meniscus of the collection medium 3A in the tip. The shape of the surface of the collecting medium can be influenced by appropriate measures. Thus, a high affinity of the inner surface of the tip with respect to the collection medium 3A causes an inwardly curved meniscus, as in Fig. 5B is shown. Conversely, an outwardly curved meniscus can be achieved by a reduced affinity of the inner surfaces of the tip with respect to the collection medium 3A.

Of course it is also possible, based on Fig. 5B use 3B to combine with a specific adjustment of the surface affinity. Thus, on the geometry or the surface condition of the collecting device 3, the shape of the carrier 2 presented surface of the collecting medium 3 can be influenced in a targeted manner.

Fig. 6 schematically illustrates a monitoring of the collecting medium 3A to the collecting device 3. The in Fig. 6 schematically illustrated monitoring means comprise a light barrier, which has a light source 8A and a sensor 8B. The drop of the collection medium 3A is positioned in the light path so that the signal strength detected by the sensor 8B changes depending on the load of the drop of objects. Furthermore, it can also be checked in this way whether a drop of collecting medium 3A is present at the tip of the collecting device 3. The latter can be used to ensure that sufficient collecting medium 3A is present at the tip of the collecting device 3 before the laser-induced transport process. Furthermore, in this way the basis of Fig. 4 illustrated dispensing operation of the collecting medium 3A are monitored in the target container 5.

Alternative embodiments of the monitoring means may be based, for example, on an optical image of the collecting medium 3A with automatic image processing or on an ultrasound-based monitoring method.

Furthermore, there are many possibilities to design the transport of the separated objects by means of the collecting medium 3A. Thus, alternatively or in addition to the basis of 3 and 4 explained drop-shaped transfer of the collecting medium 3A in the target container 5 a variety of other approaches are followed. These may include, for example, conveying the collecting medium 3A, sucking off the collecting medium 3A or otherwise causing flow movement. Furthermore, the collecting medium 3A can be transported on special chips by surface acoustic waves. Thus, for certain applications, direct supply of the collecting medium 3A with the objects 4 'contained therein onto an analysis chip is possible and advantageous.

Furthermore, the previously described concept of catapulting onto or into a liquid collecting medium is by no means limited to a stationary collecting medium, for example in the form of a drop. For example, it is also conceivable to have a continuous flow of Provide collecting medium into which the object or the objects are catapulted.

The illustrated solution for handling microdissected biological objects offers a number of advantages. Thus, it ensures low material consumption, easy automation, the possibility of high throughput, a reduced risk of contamination and lower storage costs for consumables. For a large number of preparation and analysis processes, a considerably more effective overall procedure is made possible. It is possible to dispense with any autoclaving processes of consumable products used in the conventional methods, since in particular no collecting containers or collecting substrates specially provided for this purpose are necessary. Accurate fluid guidance ensures high accuracy and reliability of examinations and preparations.

Claims (22)

1. A method of handling articles,
   wherein an article (4') is present on a carrier (2) and
   wherein the article (4') is conveyed from the carrier (2) to a collecting medium (3A) by a laser-induced conveying process,
   wherein the collecting medium (3A) is in a liquid state and is held by a collecting apparatus (3),
   characterized in that the collecting medium (3A) is held in the form of a drop at a tip of the collecting apparatus (3).
2. A method according to Claim 1, characterized in that the article (4') is transferred with the collecting medium (3A) to a destination (5) after the laser-induced conveying process.
3. A method according to Claim 2, characterized in that the transfer of the article (4') to the destination (5) includes a conveying of the collecting medium (3A).
4. A method according to Claim 2 or 3, characterized in that the transfer of the article (4') to the destination (5) includes effecting a flow movement of the collecting medium (3A).
5. A method according to any one of Claims 2 to 4, characterized in that the transfer of the article (4') to the destination (5) includes a discharge of the collecting medium (3A) in the form of a drop.
6. A method according to any one of Claims 2 to 5, characterized in that the transfer of the article (4') to the destination includes a sucking away of the collecting medium (3A).
7. A method according to any one of Claims 2 to 6, characterized in that the transfer of the article (4') to the destination (5) includes a movement of the collecting apparatus (3) relative to the destination (5).
8. A method according to any one of Claims 2 to 7, characterized in that the transfer of the article (4') to the destination (5) includes a supply of further collecting medium (3A) to the collecting medium (3A) with the article (4').
9. A method according to any one of Claims 2 to 8, characterized in that the transfer of the article (4') to the destination (5) takes place automatically.
10. A method according to any one of the preceding Claims, characterized in that the collecting medium (3A) is held on the collecting apparatus (3) by adhesion and/or surface tension.
11. A method according to Claim 10, characterized in that the shaping of a surface of the collecting medium (3A) presented to the carrier (2) is influenced in a purposeful manner by the geometry of the collecting apparatus (3).
12. A method according to Claim 10 or 11, characterized in that the shaping of a surface of the collecting medium (3A) presented to the carrier (2) is influenced in a purposeful manner by the surface characteristics of the collecting apparatus (3).
13. A method according to any one of the preceding Claims, characterized in that the collecting medium (3A) is selected in dependence upon a subsequent processing step for the article (4').
14. A method according to any one of the preceding Claims, characterized in that the article (4') is separated by laser radiation from a mass (4) present on the carrier (2).
15. A method according to any one of the preceding Claims, characterized by checking the result of the laser-induced conveying process by monitoring the collecting medium (3A).
16. A method according to Claim 15, characterized in that the monitoring is carried out on the basis of an optical signal processing.
17. A method according to Claim 15 or 16, characterized in that the checking is carried out on the basis of acoustic signals in the ultrasonic range.
18. An apparatus for handling articles,
    wherein an article (4') is present on a carrier (2) and
    wherein the article (4') is conveyed from the carrier (2) to a collecting apparatus (3) by a laser-induced conveying process, comprising:

    the collecting apparatus (3) for holding a collecting medium (3A) which is in a liquid state,

    a holding apparatus (15) for holding the carrier (2),

    a laser arrangement (7, 9) for performing the laser-induced conveying process,

    characterized in that the collecting apparatus (3) comprises a tip which is designed to hold the collecting medium (3A) in the form of a drop.
19. An apparatus according to Claim 18, characterized by imaging means (10, 11) for producing an image of the carrier (2).
20. An apparatus according to Claim 18 or 19, characterized in that the tip comprises an opening for the discharge of the collecting medium (3A).
21. An apparatus according to Claim 20, characterized in that an insert (3B), which provides an additional surface for holding the collecting medium (3A), is provided in the opening in the tip.
22. An apparatus according to any one of Claims 18 to 21, characterized in that the apparatus is designed to perform the method according to any one of Claims 1 to 17.

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